1. Field of the Invention
This invention relates to novel apparatus and methods for the collection of bodily fluids, such as interstitial fluids, from the body of an animal, such as a mammal. The fluids so collected may then be analyzed for biological or medical purposes, such as, for example, disease and health management activities. More particularly, this invention provides novel apparatus and methods for the collection of large quantities of interstitial fluids from areas of the skin where the stratum corneum has been breached.
2. Discussion of the Art
The stratum corneum is the outer horny layer of the skin comprising a complex structure of compact keratinized cell remnants separated by lipid domains. In humans, the stratum corneum typically has a thickness of about 10 xcexcm to about 30 xcexcm and overlays the epidermal layer, which itself has a thickness of on the order of about 100 xcexcm. The dermal layer, found below the epidermal layer, contains, among other things, capillary networks through which blood flows.
It has been proposed that interstitial fluids can be obtained from the epidermal layer in a minimally invasive procedure by stripping away the stratum corneum to expose the epidermal layer and thereafter collecting interstitial fluids from the epidermis. Repeated application and removal of cellophane tape to the same location can be used to strip away the stratum corneum to expose the epidermal layer for the collection of interstitial fluids. Another technique available for the collection of interstitial fluids involves inserting a micro needle into the epidermal layer to allow fluids to be wicked up out of the body for deposit onto a membrane collection strip. This approach, however, requires precise insertion of the micro needle, oftentimes by trained medical personnel, and also results in biohazardous xe2x80x9csharpsxe2x80x9d.
Another series of techniques for collecting interstitial fluids are described in PCT Patent Application, Serial No. PCT/US96113865, published on Mar. 6, 1997, International Publication No. WO97107734 and the prior art cited therein (hereinafter referred to as the xe2x80x9cPCT applicationxe2x80x9d). The PCT application describes the use of energies at various wavelengths and frequencies to form micropores through the stratum corneum to a depth that exposes the epidermal layer. Methods to form such micropores include laser, sonic energy, and thermal energy, with or without the use of dyes or other energy absorbing materials to assist in the ablation and removal of the stratum corneum. In the PCT application, interstitial fluids are described as exuding from the epidermis after microporation of the stratum corneum. In addition, to induce fluid flow, a vacuum (10 to 12 inches of Hg) can be applied to the microporation sites (Examples 14 and 39 of the PCT application described above). Example 14 describes the use of the recovered fluids for analysis of biological materials, such as glucose levels. In Example 39, the use of a vacuum (i.e., a negative pressure) and ultrasound was said to produce an increase in the quantity of recovered interstitial fluid when compared with the use of vacuum alone.
In connection with the vacuum assist approach described in that PCT application, the volume collected is a function of the number of micropores, the level of vacuum, and the length of time the vacuum is applied. However, the techniques disclosed in the PCT application referred to above suffer from several disadvantages. First, even when all variables are optimized, the quantity of interstitial fluids obtained from the micropores in a short time period may not be sufficient to utilize in various medically related testing procedures. Second, increasing the applied vacuum above about 13 inches Hg (about xe2x88x926.5 psig) can result in visible hematomas of the skin and patient discomfort. Moreover, the use of vacuum assistance increases the evaporation of the fluids under extraction and requires a substantially air-tight seal around the microporation site, which can oftentimes be difficult to achieve, even in a clinical setting. Finally, this technique also requires vacuum pumps and attendant fixtures, which can be expensive to acquire and maintain.
These and other disadvantages of the prior art are overcome by the apparatus and method of the present invention. In particular, the present invention provides apparatus and methods that allow the collection of large quantities of bodily fluids, such as interstitial fluids, from the epidermal layer over short periods of time, when compared with the amounts collectable through prior art techniques, without the need for vacuum assist devices. The apparatus and methods are inexpensive to fabricate, easy to use, and present minimal discomfort to the patient.
In the present invention, it has been discovered that increased amounts of interstitial fluids can be collected from micropores formed through the stratum corneum and extending into the epidermal layer by using a novel cup-shaped pressure head applied to the area of the skin surrounding the micropores. The pressure head is applied under a positive pressure, the force of which may fall within the broad range of about 1 to about 11 pounds, preferably from about 3 to about 11 pounds, with about 4 to about 9 pounds being preferred. The pressure head includes an aperture of diameter sufficient to surround the micropores, together with a reservoir volume in which the fluids may be collected and maintained and from which the fluids may be sampled or removed. The positive pressure may also be conveniently applied using the pressure head, with collection of fluids being carried out with separate apparatus, such as a capillary tube, an absorbent material, or other suitable device. The head may be housed in a holder having an air ram or other mechanism to provide variable pressure to the head when the head is placed on a patient""s skin. The method of the present invention includes forming a breach through the stratum corneum and into the epidermal layer, followed by the application of a positive pressure to the area surrounding the microporation site to cause interstitial fluids to exude therefrom. The interstitial fluids are then collected.